| 1. |
- Bemark, Mats, et al.
(författare)
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Purification and characterization of a protein binding to the SP6 κ promoter : A potential role for CArG-box binding factor-A in κ transcription
- 1998
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258. ; 273:30, s. 18881-18890
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Tidskriftsartikel (refereegranskat)abstract
- A protein interacting with an A-T-rich region that is a positive control element within the SP6 κ promoter was purified and identified as CArG-box binding factor-A. The purified protein was shown to interact specifically with the coding strand of single-stranded DNA and, with lower affinity, with double-stranded DNA. A mutation that inhibited binding of the protein to the A-T-rich region also aborted the transcriptional stimulatory effect of the region. Two Ets proteins, PU.1 and elf-1, that have previously been shown to bind to an adjacent DNA element were shown to physically interact with CArG- box binding factor.A. An antiserum raised against the protein recognized two different forms indicating either that different splice-forms of CArG-box binding factor-A are expressed, or that the protein is subject to posttranslational modification.
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| 2. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 3. |
- Kokelj, Spela, 1992, et al.
(författare)
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Activation of the Complement and Coagulation Systems in the Small Airways in Asthma
- 2023
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Ingår i: Respiration. - : S. Karger. - 0025-7931 .- 1423-0356. ; 102:8, s. 621-631
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have shown the importance of the complement and coagulation systems in the pathogenesis of asthma. Objectives: We explored whether we could detect differentially abundant complement and coagulation proteins in the samples obtained from the small airway lining fluid by collection of exhaled particles in patients with asthma and whether these proteins are associated with small airway dysfunction and asthma control. Method: Exhaled particles were obtained from 20 subjects with asthma and 10 healthy controls (HC) with the PExA method and analysed with the SOMAscan proteomics platform. Lung function was assessed by nitrogen multiple breath washout test and spirometry. Results: 53 proteins associated with the complement and coagulation systems were included in the analysis. Nine of those proteins were differentially abundant in subjects with asthma as compared to HC, and C3 was significantly higher in inadequately controlled asthma as compared to well-controlled asthma. Several proteins were associated with physiological tests assessing small airways. Conclusions: The study highlights the role of the local activation of the complement and coagulation systems in the small airway lining fluid in asthma and their association with both asthma control and small airway dysfunction. The findings highlight the potential of complement factors as biomarkers to identify different sub-groups among patients with asthma that could potentially benefit from a therapeutic approach targeting the complement system.
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| 4. |
- Kokelj, Spela, 1992, et al.
(författare)
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Smoking induces sex-specific changes in the small airway proteome
- 2021
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Ingår i: Respiratory Research. - : BioMed Central. - 1465-9921 .- 1465-993X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Cigarette smoke triggers many cellular and signaling responses in the lung and the resulting inflammation plays a central role in smoke-related lung diseases, such as COPD. We explored the effects of smoking on the small airway proteome in samples obtained by collection of exhaled particles with the aim to identify specific proteins dysregulated by smoking. Methods Exhaled particles were obtained from 38 current smokers, 47 former smokers and 22 healthy controls with the PExA method. 120 ng of sample was collected from individual subjects and analyzed with the SOMAscan proteomics platform. General linear model-based statistics were performed. Results Two hundred and three proteins were detected in at least half of 107 total samples. Active smoking exerted a significant impact on the protein composition of respiratory tract lining fluid (RTLF), with 81 proteins altered in current smokers compared to never smokers (p < 0.05, q < 0.124). Among the proteins most clearly discriminating between current and never smokers were sRAGE, FSTL3, SPOCK2 and protein S, all of them being less abundant in current smokers. Analysis stratified for sex unveiled sex differences with more pronounced proteomic alterations due to active smoking in females than males. Proteins whose abundance was altered by active smoking in women were to a larger extent related to the complement system. The small airway protein profile of former smokers appeared to be more similar to that observed in never smokers. Conclusions The study shows that smoking has a strong impact on protein expression in the small airways, and that smoking affects men and women differently, suggesting PExA sampling combined with high sensitivity protein analysis offers a promising platform for early detection of COPD and identification of novel COPD drug targets.
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| 5. |
- Najafinobar, Neda, 1985, et al.
(författare)
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ToF-SIMS mediated analysis of human lung tissue reveals increased iron deposition in COPD (GOLD IV) patients
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease that is currently the third leading cause of death worldwide. Recent reports have indicated that dysfunctional iron handling in the lungs of COPD patients may be one contributing factor. However, a number of these studies have been limited to the qualitative assessment of iron levels through histochemical staining or to the expression levels of iron-carrier proteins in cells or bronchoalveolar lavage fluid. In this study, we have used time of flight secondary ion mass spectrometry (ToF-SIMS) to visualize and relatively quantify iron accumulation in lung tissue sections of healthy donors versus severe COPD patients. An IONTOF 5 instrument was used to perform the analysis, and further multivariate analysis was used to analyze the data. An orthogonal partial least squares discriminant analysis (OPLS-DA) score plot revealed good separation between the two groups. This separation was primarily attributed to differences in iron content, as well as differences in other chemical signals possibly associated with lipid species. Further, relative quantitative analysis revealed twelve times higher iron levels in lung tissue sections of COPD patients when compared to healthy donors. In addition, iron accumulation observed within the cells was heterogeneously distributed, indicating cellular compartmentalization.
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| 6. |
- Olsson, Henric, et al.
(författare)
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Presence of a novel form of phosphatidylinositol 4-kinase in rat liver
- 1995
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Ingår i: FEBS Letters. - 1873-3468. ; 361:2-3, s. 282-286
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Tidskriftsartikel (refereegranskat)abstract
- Rat liver microsomes contain two distinct forms of PtdIns 4-kinase which were resolved by heparin-Sepharose chromatography. One enzyme was identified as the type II PtdIns kinase previously isolated from exocytotic vesicles. The other enzyme, however, was a novel PtdIns 4-kinase isoform with properties differing from any other PtdIns kinase so far characterized. Both kinases were recognized by a monoclonal antibody specific for type II PtdIns 4-kinase, but the novel enzyme was considerably less sensitive to inhibition by adenosine and Ca2+ than type II enzymes, and in addition was specifically inhibited by submillimolar concentrations of dithioerythritol. The presence of a novel PtdIns 4-kinase isoform in rat liver raises the question of whether this enzyme is unique for this organ or whether it has a more widespread distribution but so far has avoided detection.
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| 7. |
- Olsson, Viktoria, et al.
(författare)
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Meat that has been frozen and thawed : compatible with high gastronomic standards?
- 2022
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Konferensbidrag (refereegranskat)abstract
- A long-term strategic work entailing animal- and environmental consideration has led to added values in the Swedish meat production. Today, meat handling may comprise logistics that include storage of frozen raw material to even out geographical and seasonal variations in demand. This is the case for the culturally significant Christmas ham that can be preserved through freezing before preparation just in time for the festive season. The formation of ice crystals during freezing damages the cell structure and concentrates the solutes in the meat (Leygonie et al. 2012; Bao et al., 2021). Improper thawing can result in quality losses, such as texture and colour changes, water loss, and denaturation and oxidation of myofibrillar proteins. This affects the eating quality and nutritional value of the meat negatively. At Kristianstad University, the effect of air- compared to microwave thawing was recently investigated in a pilot study and the water-holding ability was shown to be affected by thawing method (Nilsson & Lilja, 2021). As meat is very resource-demanding, all production processes must be optimized to reduce energy consumption and waste. Further, innovative preservation techniques like high-pressure processing (HPP), by which a product is nonthermally treated at high pressures by means of a liquid transmitter, can be applied to improve product quality. There are scientifically unaddressed questions regarding the effect of these technologies on sensory perception and consumer acceptance. Applied, challengedriven research is also lacking. We want to address this in a new project founded by the Knowledge Foundation to investigate if meat that has been frozen and thawed can be compatible with high gastronomic standards.
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| 8. |
- Ramos-Ramirez, Patricia, et al.
(författare)
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House Dust Mite and Cat Dander Extract Induce Asthma-Like Histopathology with an Increase of Mucosal Mast Cells in a Guinea Pig Model
- 2023
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Ingår i: Journal of Immunology Research. - : Hindawi Publishing Corporation. - 2314-8861 .- 2314-7156. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- Background. Asthma is a chronic inflammatory disease with structural changes in the lungs defined as airway remodelling. Mast cell responses are important in asthma as they, upon activation, release mediators inducing bronchoconstriction, inflammatory cell recruitment, and often remodelling of the airways. As guinea pigs exhibit anatomical, physiological, and pharmacological features resembling human airways, including mast cell distribution and mediator release, we evaluated the effect of extracts from two common allergens, house dust mite (HDM) and cat dander (CDE), on histopathological changes and the composition of tryptase- and chymase-positive mast cells in the guinea pig lungs. Methods. Guinea pigs were exposed intranasally to HDM or CDE for 4, 8, and 12 weeks, and airway histology was examined at each time point. Hematoxylin and eosin, Picro-Sirius Red, and Periodic Acid-Schiff staining were performed to evaluate airway inflammation, collagen deposition, and mucus-producing cells. In addition, Astra blue and immunostaining against tryptase and chymase were used to visualize mast cells. Results. Repetitive administration of HDM or CDE led to the accumulation of inflammatory cells into the proximal and distal airways as well as increased airway smooth muscle mass. HDM exposure caused subepithelial collagen deposition and mucus cell hyperplasia at all three time points, whereas CDE exposure only caused these effects at 8 and 12 weeks. Both HDM and CDE induced a substantial increase in mast cells after 8 and 12 weeks of challenges. This increase was primarily due to mast cells expressing tryptase, but not chymase, thus indicating mucosal mast cells. Conclusions. We here show that exposure to HDM and CDE elicits asthma-like histopathology in guinea pigs with infiltration of inflammatory cells, airway remodelling, and accumulation of primarily mucosal mast cells. The results together encourage the use of HDM and CDE allergens for the stimulation of a clinically relevant asthma model in guinea pigs.
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| 9. |
- Rosenberg, Krisztina, et al.
(författare)
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Cartilage oligomeric matrix protein shows high affinity zinc-dependent interaction with triple helical collagen
- 1998
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 273:32, s. 20397-20403
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage and tendon extracellular matrices are composed of collagens, proteoglycans, and a number of noncollagenous proteins. Cartilage oligomeric matrix protein (COMP) is a prominent such protein, structurally related to the thrombospondins. We found that native COMP binds to collagen I/II and procollagen I/II and that the interaction is dependent on the divalent cations Zn2+ or Ni2+, whereas Ca2+, Mg2+, and Mn2+ did not promote binding. Using a solid phase assay, Scatchard analysis identified one class of binding site with a dissociation constant (Kd) close to 1.5 nM in the presence of Zn2+. The results were confirmed by studies using surface plasmon resonance. Furthermore, metal chelate chromatography demonstrated that COMP bound Zn2+ and Ni2+. Electron microscopy showed that the interaction occurred at four defined sites on the 300-nm collagen and procollagen molecules. Two were located close to each end, and two at 126 and 206 nm, respectively, from the C-terminal. COMP interacted via its C-terminal globular domain and significantly only in the presence of Zn2+.
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| 10. |
- Simonsson, Moa, et al.
(författare)
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Development and Validation of a Novel Risk Score for In-Hospital Major Bleeding in Acute Myocardial Infarction : The SWEDEHEART Score
- 2019
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Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Background – Bleeding risk stratification in acute coronary syndrome is of highest clinical interest but current risk scores have limitations. We sought to develop and validate a new in-hospital bleeding risk score for patients with acute myocardial infarction.Methods and Results – From the nationwide SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register, 97,597 patients with acute myocardial infarction enrolled from 2009 until 2014 were selected. A full model with 23 predictor variables and 8 interaction terms was fitted using logistic regression. The full model was approximated by a model with 5 predictors and 1 interaction term. Calibration, discrimination, and clinical utility was evaluated and compared with the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) scores. Internal and temporal validity was assessed. In-hospital major bleeding, defined as fatal, intracranial, or requiring surgery or blood transfusion, occurred in 1356 patients (1.4%). The 5 predictors in the approximate model that constituted the SWEDEHEART score were hemoglobin, age, sex, creatinine, and Creactive protein. The ACTION and CRUSADE scores were poorly calibrated in the derivation cohort and therefore were recalibrated. The SWEDEHEART score showed higher discriminative ability than both recalibrated scores, overall (C-index 0.80 versus 0.73/0.72) and in all predefined subgroups. Decision curve analysis demonstrated consistently positive and higher net benefit for the SWEDEHEART score compared with both recalibrated scores across all clinically relevant decision thresholds. The original ACTION and CRUSADE scores showed negative net benefit.Conclusions – The 5-item SWEDEHEART score discriminates in-hospital major bleeding in patients with acute myocardial infarction and has superior model performance compared with the recalibrated ACTION and CRUSADE scores.
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| 11. |
- Sjöstedt, Victoria, et al.
(författare)
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Klimatanpassning av bostäder och bostadsområden : resultat från ett samarbetsprojekt mellan CEC och Riksbyggen
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport är en sammanställning av kunskap som genererats inom ramen för ett samarbetsprojekt mellan Centrum för miljö- och klimatforskning (CEC) vid Lundsuniversitet och Riksbyggen om klimatanpassning av bostäder och bostadsområden iSverige. Samarbetsprojektet byggde på utveckling och handledning av fem styckenmasteruppsatser vid Tillämpad klimatstrategi-programmet vid Lunds universitet,mellan november 2014 och juni 2015. De deltagande studenterna utvecklade sinauppsatser i dialog med Riksbyggen, och ett flertal av studenterna använde Riksbyggensbostadsbestånd som konkreta fallstudier. I denna rapport diskuteras de resultatsom framkommit i masteruppsatserna, med fokus på klimatrelaterad riskkartering,metoder för klimatanpassningsåtgärder, kunskapsunderlag, samt samverkan ochdeltagande. Syntesrapporten levererar inspirationsmaterial för Riksbyggens vidarearbete med klimatanpassning av bostadsrättsföreningar. Förslag på sätt att hantera klimatanpassningsproblematik i bostadssektorn läggs fram, vilka inkluderar utökad klimatrelaterad riskkartering, skräddarsydda åtgärdspaket, intern och externkommunikation av klimatrelaterade risker och anpassningsåtgärder, samt nya samarbetskonstellationer. Samarbetet mellan CEC och Riksbyggen tog tillvara på denpotential som finns i studentarbeten och skapade länkar mellan utbildning, forskningoch näringsliv. I rapporten förs en diskussion kring sätt att vidareutveckla dennasamarbetsmodell för att förnya och verka kvalitetshöjande för grundutbildningen.Rapporten identifierar även relevanta teman för nya masterprojekt, samt konkretaforskningsbehov kring kunskapsöverföring mellan aktörer och nivåer; samarbetemellan boende, fastighetsägare, myndigheter, konsulter och försäkringsbolag kringriskkartering och anpassningsåtgärder; kommunikationsinsatser för ökad acceptans föranpassningsåtgärder; samt juridiska och ekonomiska incitamentsstrukturer. Dessa ärviktiga områden att adressera i framtida forskningsinsatser för att stödja implementeringav utökad klimatrelaterad riskkartering och anpassningsåtgärder i bostadssektorn.
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| 12. |
- Skoglund, Thomas, 1969, et al.
(författare)
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A method for 2D reconstruction of intracellularly labeled neurons from sequential sections.
- 1994
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Ingår i: Journal of neuroscience methods. - 0165-0270. ; 53:2, s. 199-202
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Tidskriftsartikel (refereegranskat)abstract
- A technique for 2D reconstruction of intracellularly labeled neurons from sequential sections is described. The system consists of a Charged Coupled Device-camera mounted on a microscope, a videomixer and a IBM-compatible PC with a framegrabber. The neurons (interneurons from the spinal cord of the cat) were labeled iontophoretically by horshradish peroxidase and subsequently cut in 60 microns sections. The sections were aligned using the video mixer by fitting the cut dendrites and axon from one section with their counterparts in the following section. The images were then digitized in the PC where they were fused to create a superimposed picture of the aligned parts of the neuron; a 2D reconstruction was created.
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| 13. |
- Torngren, Kristina, et al.
(författare)
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Association of coronary calcium score with endothelial dysfunction and arterial stiffness
- 2020
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 313, s. 70-75
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The aim of the study was to determine potential associations between endothelial dysfunction and arterial stiffness, measured by peripheral arterial tonometry, and coronary artery calcium score (CACS) assessed by computed tomography (CT). Methods and results: The BIG3 study is a prospective longitudinal, non-interventional, pulmonary-cardiovascular cohort study exploring the three major smoking-induced diseases: cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, in a 45–75 aged cohort (mean 62 years), enriched in smokers. Computed tomography of the chest with assessment of CACS was performed in a selected subset of the participants (n = 2080). Peripheral arterial tonometry (EndoPAT) was used to assess endothelial function and arterial stiffness measured as reactive hyperaemia index (RHI) and augmentation index (AI), respectively. We observed significant associations of CACS, endothelial dysfunction, and arterial stiffness with several risk factors for coronary heart disease including age, sex, BMI, diabetes mellitus, and blood pressure. There was significant association of CACS, classified into three levels of severity, with RHI and AI (p = 0.0005 and p = 0.0009, respectively). For groups of increasing CACS (0, 1–400 and > 400 Agatston score), RHI decreased from median 1.89 (1.58–2.39), and 1.93 (1.62–2.41) to 1.77 (1.51–2.10). AI increased from median 14.3 (5.7–25.2), and 16.4 (8.1–27.6) to 18.0 (9.1–29.2). RHI, but not AI, remained significantly associated with CACS after risk factors adjustment. Conclusions: In this large study of coronary artery calcium and vascular function, we found an association between CACS and both endothelial dysfunction and arterial stiffness, indicating that they may reflect similar mechanisms for development of cardiovascular disease.
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| 14. |
- Wollmer, Per, et al.
(författare)
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Within-session reproducibility of forced oscillometry
- 2021
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:5, s. 401-407
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The forced oscillation technique (FOT) provides detailed information about the mechanics of the respiratory system, while requiring minimal co-operation by the patient. FOT may be abnormal in subjects with normal spirometry and appears to be more closely related to airway symptoms. It is, therefore, attractive in epidemiological studies, where a large number of different examinations are made in each subjects in a short period of time. Current technical standards recommend the mean of three consecutive measurements to be used, but there is limited information regarding within-session variability of FOT measurements.OBJECTIVE: The purpose of this study was to examine the within-session variability in FOT measurements in a large, population-based sample.METHODS: We performed three consecutive FOT measurements in 700 subjects using the impulse oscillometry system. The first measurement was compared to the mean of three measurements for resistance at 5 and 20 Hz (R5 and R20, respectively), R5-R20, reactance at 5 Hz (X5) and resonant frequency (fres ).RESULTS: The differences between the first and the mean of three measurements (median, interquartile range) were minimal, for example 0.002, -0.008 to 0.014 kPa L-1 s for R5 and -0.001, -0.008 to 0.005 kPa L-1 s for X5. Findings were numerically similar for men and women as well as for subjects with and without airflow obstruction at spirometry.CONCLUSIONS: We conclude that, whereas in clinical situations, three FOT measurements are to be preferred, a single measurement may suffice in epidemiological studies.
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